Hammett Σm Research Articles

Investigation of substituent effect on O–C bond dissociation enthalpy of methoxy group in meta- and para-substituted anisoles

This paper is focused on the theoretical investigation of O–C Bond Dissociation Enthalpy (BDE) of methoxy OCH3 group in 15 meta- and 15 para-substituted anisoles in gas phase, non-polar environment, and water. Density Functional Theory (DFT) calculations were carried out using M06-2X functional and 6-311++G(d,p) basis set. Obtained BDEs were correlated with Brown and Okamoto σp+ and Hammett σm constants representing commonly used descriptors of electron-donating or electron-withdrawing substituent effect. Obtained linear dependences allow the prediction of substituent effect on BDE using σp+ and σm constants. Calculated reaction enthalpies were also compared with available experimental and theoretical ab initio G4 values. Found results suggest that employed method may provide reliable thermochemistry data for demethylation of naturally occurring (poly)phenolic compounds, as well. In all studied environments, substituent induced changes in O–C BDE can be considered equal to those observed for the dissociation of phenolic O–H bond of substituted phenols.

Hammett Relationship in Oxidase-Mimicking Metal-Organic Frameworks Revealed through a Protein-Engineering-Inspired Strategy.

While the unique physicochemical properties of nanomaterials that enable regulation of nanozyme activities are demonstrated in many systems, quantitative relationships between the nanomaterials structure and their enzymatic activities remain poorly understood, due to the heterogeneity of compositions and active sites in these nanomaterials. Here, inspired by metalloenzymes with well-defined metal-ligand coordination, a set of substituted metal-organic frameworks (MOFs) with similar coordination is employed to investigate the relationship between structure and oxidase-mimicking activity. Both experimental results and density functional theory calculations reveal a Hammett-type structure-activity linear free energy relationship (H-SALR) of MIL-53(Fe) (MIL = Materials of Institute Lavoisier) nanozymes, in which increasing the Hammett σm value with electron-withdrawing ligands increases the oxidase-mimicking activity. As a result, MIL-53(Fe) NO2 with the strongest electron-withdrawing NO2 substituent shows a tenfold higher activity than the unsubstituted MIL-53(Fe). Furthermore, the generality of H-SALR is demonstrated for a range of substrates, one other metal (Cr), and even one other MOF type (MIL-101). Such biologically inspired quantitative studies demonstrate that it is possible to identify quantitative structure-activity relationships of nanozymes, and to provide detailed insight into the catalytic mechanisms as those in native enzymes, making it possible to use these relationships to develop high-performance nanomaterials.

Catechol reactivity: Synthesis of dopamine derivatives substituted at the 6-position

ABSTRACTDopamine is a ubiquitous neurotransmitter essential in the proper functioning of the human body. In addition to this critical role, the catecholamine core has shown utility as a scaffold for numerous drugs and in other applications, like metal detection and adhesive materials. Substituents at the 6-position of dopamine’s catechol core can modulate its stereoelectronic properties, the acidity of its phenolic hydroxyl groups, and the overall hydrophobicity of the molecule. Herein, we report the synthesis of a series of four novel dopamine analogues substituted at the 6-position of catechol core. The 1H NMR chemical shift of the aromatic proton meta to the substituent correlated strongly with the Hammett σm constant, confirming the electronic properties of substituents.

Electronic excited state redox properties for BODIPY dyes predicted from Hammett constants: estimating the driving force of photoinduced electron transfer.

Here we formulate equations based solely on empirical Hammett substituent constants to predict the redox potentials for the electronic excited state of boron-dipyrromethene (BODIPY) dyes. We utilized computational, spectroscopic, and electrochemical techniques toward characterizing the effect of substitution at the positions C2, C6, and C8 of the 1,3,5,7-tetramethyl BODIPY core. Working with a library of 100 BODIPY dyes, we found that highest occupied molecular orbital (HOMO) energies calculated at the B3LYP 6-31g(d) level correlated linearly with the Hammett σm value for substituents at position C8 and with Hammett σp values for substituents at positions C2 and C6. In turn, we observed that LUMO energies correlated linearly with Hammett σp at position C8 and with Hammett σm at positions C2 and C6. Focusing on a subset of 26 dyes for which reduction potentials were either previously available or measured herein and ranged from -1.84 to -0.52 V (a full 1.3 V), we found a linear relationship between redox potentials in acetonitrile and HOMO and lowest unoccupied molecule orbital (LUMO) energies determined via density functional theory (DFT). A linear correlation was thus ultimately established between redox potentials in acetonitrile and Hammett substituent constants. Combining this with equations derived for the linear relationship existing between the zero vibrational energy of the excited BODIPY and Hammett substituent constants enabled us to provide the parameters toward predicting the oxidizing/reducing power of photoexcited 1,3,5,7,-tetramethyl BODIPY dyes in their singlet excited state.

Prediction of ortho substituent effect in alkaline hydrolysis of phenyl esters of substituted benzoic acids in aqueous acetonitrile

Abstract The second-order rate constants k for the alkaline hydrolysis of phenyl esters of meta-, para- and ortho-substituted benzoic acids, X-C6H4CO2C6H5, in aqueous 50.9% acetonitrile have been measured spectrophotometrically at 25°C. The log k values for meta and para derivatives correlated well with the Hammett σm,p substituent constants. The log k values for ortho-substituted phenyl benzoates showed good correlations with the Charton equation, containing the inductive, σI, resonance, σ○ R, and steric, E s B, and Charton υ substituent constants. For ortho derivatives the predicted (log k X)calc values were calculated with equation (log k ortho)calc = (log k H AN)exp + 0.059 + 2.19σI + 0.304σ○ R + 2.79E s B − 0.0164ΔEσI — 0.0854ΔEσ○ R, where DE is the solvent electrophilicity, ΔE = E AN — E H20 = −5.84 for aqueous 50.9% acetonitrile. The predicted (log k X)calc values for phenyl ortho-, meta- and para-substituted benzoates in aqueous 50.9% acetonitrile at 25°C precisely coincided with the experimental log k values determined in the present work. The substituent effects from the benzoyl moiety and aryl moiety were compared by correlating the log k values for the alkaline hydrolysis of phenyl esters of substituted benzoic acids, X-C6H4CO2C6H5, in various media with the corresponding log k values for substituted phenyl benzoates, C6H5CO2C6H4-X.

Probing Substituent Effects in Aryl−Aryl Interactions Using Stereoselective Diels−Alder Cycloadditions

Stereoselective Diels-Alder cycloadditions that probe substituent effects in aryl-aryl sandwich complexes were studied experimentally and theoretically. Computations on model systems demonstrate that the stereoselectivity in these reactions is mediated by differential pi-stacking interactions in competing transition states. This allows relative stacking free energies of substituted and unsubstituted sandwich complexes to be derived from measured product distributions. In contrast to gas-phase computations, dispersion effects do not appear to play a significant role in the substituent effects, in accord with previous experiments. The experimental pi-stacking free energies are shown to correlate well with Hammett sigma(m) constants (r = 0.96). These substituent constants primarily provide a measure of the inductive electron-donating and -withdrawing character of the substituents, not donation into or out of the benzene pi-system. The present experimental results are most readily explained using a recently proposed model of substituent effects in the benzene sandwich dimer in which the pi-system of the substituted benzene is relatively unimportant and substituent effects arise from direct through-space interactions. Specifically, these results are the first experiments to clearly show that OMe enhances these pi-stacking interactions, despite being a pi-electron donor. This is in conflict with popular models in which substituent effects in aryl-aryl interactions are modulated by polarization of the aryl pi-system.

Acid-base interactions in some isoquinoline and quinazoline amino derivatives

Few groups of substituted 1-aminoisoquinoline, 4-amino- and 2,4-diaminoquinazoline derivatives have been examined in order to find general relationships between the basicity and a kind of substituent. pKa Values have been determined for these compounds and correlated with the original Hammett σm and σp constants. They clearly showed that the steric effects of the bulky substituents neighbouring the protonated ring nitrogen atom influence the electron transfer in such arrangements. Different tendencies in the electron transfer caused by the same groups in the position 1 of isoquinoline and position 4 of quinazoline have been also disscused. The ρ value, single crystal X-ray analysis, 15 N-NMR spectra and MNDO calculations give evidence about the electronic effects and the preferential site of protonation in such arrangements.

Substituent effects on the acidity of weak acids. 2. Calculated gas-phase acidities of substituted benzoic acids.

To investigate the origin of substituent effects on the acidity of benzoic acids, the structures of a series of substituted benzoic acids and benzoates have been calculated at the B3LYP/6-311+G* and MP2/6-311+G* theoretical levels. The vibrational frequencies were calculated using B3LYP/6-311+G* and allowed corrections for the change in zero-point energies on ionization, and the change in energy on going from 0 K (corresponding to the calculations) to 298 K. A more satisfactory agreement with the experimental values was obtained by energy calculations at the MP2/ 6-311++G* level using the above structures. The resulting Delta H(acid) values agree very well with the experimental gas-phase acidities. The energies of compounds with pi-electron-accepting or -releasing substituents, rotated to give the transition state geometries, provided rotational barriers that could be compared with those found for the corresponding substituted benzenes. Isodesmic reactions allowed the separate examination of the substituent effects on the energies of the acids and on the anions. Electron-withdrawing groups stabilize the benzoate anions more than they destabilize the benzoic acids. Electron-donating groups stabilize the acids and destabilize the anions by approximately equal amounts. The gas-phase acidities of meta- and para-substituted benzoic acids are linearly related. This is also found for the acidities of substituted phenylacetic acids and benzoic acids. Since direct pi-electron interactions are not possible with the phenylacetic acids, this indicates that the acidities are mainly controlled by a field effect interaction between the charge distribution in the substituted benzene ring and the negative charge of the carboxylate group. The Hammett sigma(M) and sigma(P) values are also linearly related for many small substituents from NO(2) through the halogens and to OH and NH(2). Most of the other substituents fall on a line with a different slope

Cooperative Redox Regulation of [4Fe-4S] Ferredoxin Model Arenethiolate Complexes by NH···S Hydrogen Bonds and an Aromatic C–H···S Interaction

Abstract A series of the model complexes containing ortho-substituted arenethiolato ligands, ((Et4N)2[Fe4S4(S-2-RCONHC6H4)4] {R = Ph (1), 4-MeO–C6H4 (2), and 4-F–C6H4 (3)} and (Et4N)2[Fe4S4{S-2,6-(RCONH)2C6H3}4] {R = Ph (4), 4-MeO–C6H4 (5), and 4-F–C6H4 (6)}) was synthesized and characterized by 1H NMR, IR spectroscopy, and cyclic voltammetry. The solution structures of these complexes are discussed based on their 1H NMR T1 data and molecular-dynamics calculations. Complex 4 has a shorter distance (av. 4.3 Å) between the protons of the benzoyl group and the inorganic sulfur atom of the [4Fe-4S] cluster than the corresponding ones of 1 (av. 6.2 Å). These results indicate the C–H···S interaction between the protons of the benzoyl group and the sulfur atom of the [4Fe-4S] cluster. The [Fe4S4(SAr)4]2−/[Fe4S4(SAr)4]3−redox potential for 1 and 4 are −0.86 and −0.65 V, respectively. The difference between 1 and 4 is Δ0.21 V. This is larger than the value Δ0.11 V between [Fe4S4(S-2-t-BuCONHC6H4)4]2− (−0.91 V) and [Fe4S4{S-2,6-(t-BuCONH)2C6H3}4]2− (−0.80 V), considered to be the difference between singly and doubly NH··&middotS hydrogen-bonded complexes. The redox potentials for 1—6 follow the trend of the Hammett σm values, showing that the aromatic ring of the benzoyl group interacts with the [4Fe-4S] cluster directly. A cooperative effect between the C–H···S interaction and the NH···S hydrogen bond is thus found to regulate the redox potential of the model complexes.

A 13C NMR spectroscopy study of the structure of N-H pyrazoles and indazoles

The 13C chemical shifts and some 1H–13C coupling constants of 23 pyrazoles and indazoles are reported and discussed. The spectra were recorded in CDCl3 and in DMSO-d6 solutions and, in several cases, also in the solid state (CP/MAS technique). These data allow us to determine the tautomerism of these compounds in the solid state (usually only one tautomer) and in solution. The position of the tautomeric equilibrium is related to the Hammett σm value of the 3(5)-substituent.

Nitrogen Bridgehead Compounds. Part 81. Synthesis of 9‐(benzylidenehydrazono)‐6‐methyl‐4‐oxo‐6,7,8,9‐tetrahydro‐ and 9‐(benzylidenehydrazine)‐6‐methyl‐4‐oxo‐6,7‐dihydro‐4H‐pyrido[1,2‐a]‐pyrimidine‐3‐carboxylates

AbstractReaction of ethyl 9‐hydrazono‐6‐methyl‐4‐oxo‐6,7,8,9‐tetrahydro‐4H‐pyrido[1,2‐a]pyrimidine‐3‐carboxylate and benzaldehyde and its derivatives give a tautomeric mixture of 9‐arylidenehydrazono‐6,7,8,9‐tetrahydro‐ and 9‐arylidenehydrazine‐6,7‐dihydropyrido[1,2‐a]pyrimidine derivatives. In the same case the enhydrazine and hydrazone tautomers were separated. The structure of the products were characterised by uv, ir, 1H and 13C nmr. The equilibrium of the tautomers was affected by the substituent of the phenyl ring. A fair linear correlation exists between the logarithms of the equilibrium constants and Hammett σm and σ− constants of the substituents present on the phenyl ring.

Electrochemical determination of new Hammett σ constants corresponding to PhSe, PhTe, Se–, and Te–substituents

Hammett σm and σp constants for PhTe and Te– substituents have been derived and compared with those of the Se homologues derived from the half-wave potential shift of the first reduction step of phenylchalcogenobenzophenone and the third reduction step of symmetrical bis(cyanophenyl) chalcogenide. For the PhTe, PhSe, Te–, and Se– substituents, the σm values are 0.20, 0.20, –0.57, and –0.59 and the σp values are 0.29, 0.22, –0.72, and –0.84, respectively. The σp value of the Te– group and all of the σm values have been determined for the first time.

The electronic effect of the phenylazoxy group

Hammett σm and σp values have been determined for the phenyl-ONN-azoxy and phenyl-NNO-azoxy groups by measuring the pKa values of the phenylazoxybenzoic acids in 50% ethanol. The σp+ value for phenyl-ONN-azoxy has been evaluated both from the rate of solvolysis of 4-phenyl-ONN-azoxyphenyldimethylcarbinyl chloride in aqueous acetone, and from the rate of bromination by acidified hypobromous acid. The two values obtained differ markedly, and the variations are interpreted in terms of differences in the geometry of the transition states for the two reactions.

Structure-activity relationship in the taste effect of ribonucleotide derivatives.

Flavor enhancing activities synergistic with monosodium L-glutamate and stimulus thresholds of ribonucleotide derivatives have been correlated with their chemical structures following Hansch-Fujita's method. Regression analyses were made separately for two groups, 2-substituted inosine 5'-phosphates and S-substituted 2-mercaptoinosine 5'-phosphates. Superdelocalizability, net π-charge, Hammett σm, and hydrophobic parameter π were used in the analyses. Nuclear magnetic resonance chemical shift of the-SCH2X group and a dummy variable D, which represents a proton accepting oxygen atom at the γ- or δ-position from the sulfur atom in substituents attached to the 2-position of purine skeleton, were employed successfully in a series of 2-S-substituted derivatives. In a series of 2-substituted derivatives, it has been recognized that flavor enhancing activities are influenced by Hammett σm and electrophilic superdelocalizability at the α-position of substituents (S2a), whereas thresholds are correlated with S2a and π. In a series of 2-S-substituted derivatives, it has been shown that π, D, and electrophilic superdelocalizability of the methylene protons in the -CH2S-group of substituents play important roles in the structure-activity relationships.

Nucleophilic character of acyl radicals. Substituent effects on the homolytic acylation of protonated heteroaromatic bases

The relative rates of the homolytic acylation of protonated 2- and 4-substituted quinolines with acetyl and benzoyl radicals are reported. Orientation of products and reactivity show clear-cut nucleophilic character for the acyl radicals. The relative rates have not been correlated with the Hammett σm constants because of enhanced conjugation of the electron-releasing substituents. A much smaller effect is observed for substituted benzoyl radicals; in this case a Hammett correlation gives ρ=–0·49.

Stability Constants of Cu(II) Chelates with o-Phenylenediamine Derivatives

Abstract The stability constants of copper(II) chelates with o-phenylenediamine derivatives have been determined by the pH titration method. The measurements have been carried out at 25.0±0.1°C and μ=0.10(by KNO3). o-Phenylenediamine derivatives, which have a substituent group (CH3, CH3O, COOH, or Cl, etc.) at the 4 positions, were used as ligands. The overall stability constants of the copper chelates are of the order: CH3, CH3O, H, COO−, Cl, COOH; their values were 8.50, 8.42, 7.72, 7.06, 5.76, and 5.35 respectively. The effects of substituent groups on the stability constants have been studied. The plot of the overall stability constants against the sum of Hammett σm and σp values was found to be linear. The chelate stability and acid dissociation constants of the acido complexes of 3,4-diaminobenzoic acid were determined by the use of an augmented matrix.

Transmission of substituent effects in pyridines. Part I. Alkaline hydrolysis of some 3- and 4-substituted methyl pyridinecarboxylates

The alkaline hydrolysis of methyl 5-X-picolinates, methyl 4-X-picolinates, and methyl 5-X-nicotinates (X = NO2, Br, H, MeO, or Me2N) in methanol–water (85% w/w) is reported. In each series, the effect of the substituent and ring nitrogen are additive and the rates may be correlated with Hammett σm and σp values.

The deactivating effect of a meta‐methoxy group in the methoxydechlorination of pyridine and pyrimidine derivatives

AbstractReactivity data and the activation parameters for the methoxydechlorination of some 2‐chloro‐4‐R‐pyridines and 4‐chloro‐6‐R‐pyrimidines have been determined. A methoxy group meta with respect to the reaction site is found to be deactivating as already observed in the quinoline series. This gives further support to the hypothesis that in N‐heteroaromatic systems a conjugative interaction of an electron‐releasing substituent with the aza group (s) is a factor in modifying the nucleophilic reactivity as predicted by Hammett's σm values.

Organophosphorus chemistry. Part VI. High-resolution nuclear magnetic resonance spectra of pentafluorophenylphosphorus compounds

Nuclear magnetic resonance spectra at 14 kgauss and 35° have been obtained for the pentafluorophenylphosphorus compounds C6F5·PXY (X = Y = Cl or F; X = Cl, Y = NMe2; X = Y = NMe2; X = Y = NHBut; X = Y = Me or Et; X = Y = H), (C6F5)2PX (X = Cl, NMe2, NHBut, or H), and (C6F5)3P. Chemical shifts and coupling constants have been obtained, and some empirical correlations with Hammett σm- values of chemical shifts of fluorine nuclei meta and para to the phosphorus substituent, and of spin–spin coupling constants of fluorine nuclei meta to one another, are presented.